Glycogenolytic action of glucagon as influenced by insulin and other compounds.

The exact metabolic relationship between insulin and glucagon is still a matter of controversy. Some authors (2,3) have proposed that glucagon, like insulin, enhances the peripheral utilization of glucose. However, much evidence has been obtained which suggests that glucagon antagonizes the action of insulin. The results obtained by Thorogood and Zimmerman (4) suggested that, since alloxan-diabetic dogs required less insulin after pancreatectomy, the pancreas contained a factor which could act as an insulin antagonist. Later, de Duve et al. (5) were able to decrease considerably the amount of glucose necessary to maintain a normal blood sugar level in rabbits injected with insulin by adding insulin which contained small amounts of glucagon to the infusion. Those experiments have been confirmed and extended by Tyberghein (6), who maintained unchanged blood sugar and liver and glycogen levels in insulinized rabbits by an intravenous infusion of glucagon. Vuylsteke and de Duve (7) also demonstrated that a subcutaneous injection of glucagon decreased the action of insulin by 30 per cent. With his experiments on cross-circulation, Foa (8) came to the conclusion that glucagon is the anti-insulin hormone of the pancreas. The work of Candela (9)) Drury et al. (lo), Snedecor et al. (ll), and Pincus et al. (12) suggests that glucagon antagonizes the action of insulin in extrahepatic tissues. In order to investigate further the metabolic relationship between insulin and glucagon, the present study dealing with their action on liver slices has been carried out. Although insulin has no apparent a&ion on carbohydrates in liver tissue in vitro, it is well known that glucagon stimulates glycogenolysis in liver slices (13). It was therefore of interest to investigate whether insulin can modify the glycogenolytic action of glucagon, and if such an action is specific for insulin.